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Contrast-enhanced MRI is the method of choice for brain tumor diagnostics, despite its low specificity for tumor tissue. This study compared the contribution of MR spectroscopic imaging (MRSI) and amino acid PET to improve the detection of tumor tissue. Methods: In 30 untreated patients with suspected glioma, O -(2-[ 18 F]fluoroethyl)-l-tyrosine ( 18 F-FET) PET; 3-T MRSI with a short echo time; and fluid-attenuated inversion recovery, T2-weighted, and contrast-enhanced T1-weighted MRI were performed for stereotactic biopsy planning. Serial samples were taken along the needle trajectory, and their masks were projected to the preoperative imaging data. Each sample was individually evaluated neuropathologically. 18 F-FET uptake and the MRSI signals choline (Cho), N -acetyl-aspartate (NAA), creatine, myoinositol, and derived ratios were evaluated for each sample and classified using logistic regression. The diagnostic accuracy was evaluated by receiver operating characteristic analysis. Results: On the basis of the neuropathologic evaluation of tissue from 88 stereotactic biopsies, supplemented with 18 F-FET PET and MRSI metrics from 20 areas on the healthy-appearing contralateral hemisphere to balance the glioma/nonglioma groups, 18 F-FET PET identified glioma with the highest accuracy (area under the receiver operating characteristic curve, 0.89; 95% CI, 0.81-0.93; threshold, 1.4 × background uptake). Among the MR spectroscopic metabolites, Cho/NAA normalized to normal brain tissue showed the highest diagnostic accuracy (area under the receiver operating characteristic curve, 0.81; 95% CI, 0.71-0.88; threshold, 2.2). The combination of 18 F-FET PET and normalized Cho/NAA did not improve the diagnostic performance. Conclusion: MRI-based delineation of gliomas should preferably be supplemented by 18 F-FET PET., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

PET using O -(2- 18 F-fluoroethyl)-l-tyrosine ( 18 F-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes in 18 F-FET uptake at the rim of the resection cavity within the first 2 wk after resection of gliomas. In the present study, we evaluated pre- and postoperative 18 F-FET PET scans of glioma patients with particular emphasis on the identification of reactive changes after surgery. Methods: Forty-three patients with cerebral gliomas (9 low-grade, 34 high-grade; 9 primary tumors, 34 recurrent tumors) who had preoperative (time before surgery: median, 23 d; range, 6-44 d) and postoperative 18 F-FET PET (time after surgery: median, 14 d; range, 5-28 d) were included. PET scans (20-40 min after injection) were evaluated visually for complete or incomplete resection and compared with MRI. Changes in 18 F-FET uptake were evaluated by tumor-to-brain ratios in residual tumor and by maximum lesion-to-brain ratios near the resection cavity. Results: Visual analysis of 18 F-FET PET scans revealed complete resection in 16 of 43 patients and incomplete resection in the remaining patients. PET results were concordant with MRI in 69% of the patients. The maximum lesion-to-brain ratio for 18 F-FET uptake near the resection cavity was significantly higher than preoperative values (1.59 ± 0.36 vs. 1.14 ± 0.17; n = 43; P < 0.001). In 11 patients (26%), a flare phenomenon was observed, with a considerable increase in 18 F-FET uptake compared with preoperative values in either the residual tumor ( n = 5) or areas remote from the tumor on the preoperative PET scan ( n = 6) (2.92 ± 1.24 vs. 1.62 ± 0.75; P < 0.001). Further follow-up in 5 patients showed decreasing 18 F-FET uptake in the flare areas in 4 patients and progress in 1 patient. Conclusion: Our study confirmed that 18 F-FET PET provides valuable information for assessing the success of glioma resection. Postoperative reactive changes at the rim of the resection cavity appear to be mild. However, in 23% of the patients, a postoperative flare phenomenon was observed that warrants further investigation., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

In glioma patients, differentiation between tumor progression (TP) and treatment-related changes (TRCs) remains challenging. Difficulties in classifying imaging alterations may result in a delay or an unnecessary discontinuation of treatment. PET using O -(2- 18 F-fluoroethyl)-l-tyrosine ( 18 F-FET) has been shown to be a useful tool for detecting TP and TRCs. Methods: We retrospectively evaluated 127 consecutive patients with World Health Organization grade II-IV glioma who underwent 18 F-FET PET imaging to distinguish between TP and TRCs. 18 F-FET PET findings were verified by neuropathology (40 patients) or clinicoradiologic follow-up (87 patients). Maximum tumor-to-brain ratios (TBR max ) of 18 F-FET uptake and the slope of the time-activity curves (20-50 min after injection) were determined. The diagnostic accuracy of 18 F-FET PET parameters was evaluated by receiver-operating-characteristic analysis and χ 2 testing. The prognostic value of 18 F-FET PET was estimated using the Kaplan-Meier method. Results: TP was diagnosed in 94 patients (74%) and TRCs in 33 (26%). For differentiating TP from TRCs, receiver-operating-characteristic analysis yielded an optimal 18 F-FET TBR max cutoff of 1.95 (sensitivity, 70%; specificity, 71%; accuracy, 70%; area under the curve, 0.75 ± 0.05). The highest accuracy was achieved by a combination of TBR max and slope (sensitivity, 86%; specificity, 67%; accuracy, 81%). However, accuracy was poorer when tumors harbored isocitrate dehydrogenase ( IDH ) mutations (91% in IDH -wild-type tumors, 67% in IDH -mutant tumors, P < 0.001). 18 F-FET PET results correlated with overall survival ( P < 0.001). Conclusion: In our neurooncology department, the diagnostic performance of 18 F-FET PET was convincing but slightly inferior to that of previous reports., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: PET using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) provides important diagnostic information in addition to that from conventional MR imaging on tumor extent and activity of cerebral gliomas. Recent studies suggest that perfusion-weighted MR imaging (PWI), especially maps of regional cerebral blood volume (rCBV), may provide similar diagnostic information. In this study, we directly compared (18)F-FET PET and PWI in patients with brain tumors., Methods: Fifty-six patients with gliomas were investigated using static (18)F-FET PET and PWI. For comparison, 8 patients with meningiomas were included. We generated a set of tumor and reference volumes of interest (VOIs) based on morphologic MR imaging and transferred these VOIs to the corresponding (18)F-FET PET scans and PWI maps. From these VOIs, tumor-to-brain ratios (TBR) were calculated, and normalized histograms were generated for (18)F-FET PET and rCBV maps. Furthermore, in rCBV maps and in (18)F-FET PET scans, tumor volumes, their spatial congruence, and the distance between the local hot spots were assessed., Results: For patients with glioma, TBR was significantly higher in (18)F-FET PET than in rCBV maps (TBR, 2.28 ± 0.99 vs. 1.62 ± 1.13; P < 0.001). Histogram analysis of the VOIs revealed that (18)F-FET scans could clearly separate tumor from background. In contrast, deriving this information from rCBV maps was difficult. Tumor volumes were significantly larger in (18)F-FET PET than in rCBV maps (tumor volume, 24.3 ± 26.5 cm(3) vs. 8.9 ± 13.9 cm(3); P < 0.001). Accordingly, spatial overlap of both imaging parameters was poor (congruence, 11.0%), and mean distance between the local hot spots was 25.4 ± 16.1 mm. In meningioma patients, TBR was higher in rCBV maps than in (18)F-FET PET (TBR, 5.33 ± 2.63 vs. 2.37 ± 0.32; P < 0.001) whereas tumor volumes were comparable., Conclusion: In patients with cerebral glioma, tumor imaging with (18)F-FET PET and rCBV yields different information. (18)F-FET PET shows considerably higher TBRs and larger tumor volumes than rCBV maps. The spatial congruence of both parameters is poor. The locations of the local hot spots differ considerably. Taken together, our data show that metabolically active tumor tissue of gliomas as depicted by amino acid PET is not reflected by rCBV as measured with PWI.

Unlabelled: The aim of this study was to investigate the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET for differentiating local recurrent brain metastasis from radiation necrosis after radiation therapy because the use of contrast-enhanced MRI for this issue is often difficult., Methods: Thirty-one patients (mean age ± SD, 53 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 40) on MRI after radiation therapy of brain metastases were investigated with dynamic (18)F-FET PET. Maximum and mean tumor-to-brain ratios (TBR(max) and TBR(mean), respectively; 20-40 min after injection) of (18)F-FET uptake were determined. Time-activity curves were generated, and the time to peak (TTP) was calculated. Furthermore, time-activity curves of each lesion were assigned to one of the following curve patterns: (I) constantly increasing (18)F-FET uptake, (II) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau, and (III) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBR(max) and TBR(mean) of (18)F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or Fisher exact test for 2 × 2 contingency tables using subsequent histologic analysis (11 lesions in 11 patients) or clinical course and MRI findings (29 lesions in 20 patients) as reference., Results: Both TBR(max) and TBR(mean) were significantly higher in patients with recurrent metastasis (n = 19) than in patients with radiation necrosis (n = 21) (TBR(max), 3.2 ± 0.9 vs. 2.3 ± 0.5, P < 0.001; TBR(mean), 2.1 ± 0.4 vs. 1.8 ± 0.2, P < 0.001). The diagnostic accuracy of (18)F-FET PET for the correct identification of recurrent brain metastases reached 78% using TBR(max) (area under the ROC curve [AUC], 0.822 ± 0.07; sensitivity, 79%; specificity, 76%; cutoff, 2.55; P = 0.001), 83% using TBR(mean) (AUC, 0.851 ± 0.07; sensitivity, 74%; specificity, 90%; cutoff, 1.95; P < 0.001), and 92% for curve patterns II and III versus curve pattern I (sensitivity, 84%; specificity, 100%; P < 0.0001). The highest accuracy (93%) to diagnose local recurrent metastasis was obtained when both a TBR(mean) greater than 1.9 and curve pattern II or III were present (AUC, 0.959 ± 0.03; sensitivity, 95%; specificity, 91%; P < 0.001)., Conclusion: Our findings suggest that the combined evaluation of the TBR(mean) of (18)F-FET uptake and the pattern of the time-activity curve can differentiate local brain metastasis recurrence from radionecrosis with high accuracy. (18)F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Unlabelled: The assessment of treatment response in glioblastoma is difficult with MRI because reactive blood-brain barrier alterations with contrast enhancement can mimic tumor progression. In this study, we investigated the predictive value of PET using O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET PET) during treatment., Methods: In a prospective study, 25 patients with glioblastoma were investigated by MRI and (18)F-FET PET after surgery (MRI-/FET-1), early (7-10 d) after completion of radiochemotherapy with temozolomide (RCX) (MRI-/FET-2), and 6-8 wk later (MRI-/FET-3). Maximum and mean tumor-to-brain ratios (TBR(max) and TBR(mean), respectively) were determined by region-of-interest analyses. Furthermore, gadolinium contrast-enhancement volumes on MRI (Gd-volume) and tumor volumes in (18)F-FET PET images with a tumor-to-brain ratio greater than 1.6 (T(vol 1.6)) were calculated using threshold-based volume-of-interest analyses. The patients were grouped into responders and nonresponders according to the changes of these parameters at different cutoffs, and the influence on progression-free survival and overall survival was tested using univariate and multivariate survival analyses and by receiver-operating-characteristic analyses., Results: Early after completion of RCX, a decrease of both TBR(max) and TBR(mean) was a highly significant and independent statistical predictor for progression-free survival and overall survival. Receiver-operating-characteristic analysis showed that a decrease of the TBR(max) between FET-1 and FET-2 of more than 20% predicted favorable survival [corrected], with a sensitivity of 83% and a specificity of 67% (area under the curve, 0.75). Six to eight weeks later, the predictive value of TBR(max) and TBR(mean) was less significant, but an association between a decrease of T(vol 1.6) and PFS was noted. In contrast, Gd-volume changes had no significant predictive value for survival., Conclusion: In contrast to Gd-volumes on MRI, changes in (18)F-FET PET may be a valuable parameter to assess treatment response in glioblastoma and to predict survival time.